The WHO recently failed to accept an international standard test for the potency of IPV. The tests currently used in the USA are not ideal: ELISA tests of D Antigen do not always accurately predict neutralizing antibody responses, and tests of immunogenicity for rhesus monkeys require a sensitive species and are expensive. In FY 97, a potency test for protection of monovalent-IPV-immunized TgPVR21 mice against lethal challenge with wild-type type-3 poliovirus by was successfully extended to IPV of the other two types. Antigenic interference among the three types and a poorer immune response to IPV prepared from OPV vaccine strains than to IPV prepared from wild-type virus was demonstrated and results were published. Progress in FY 98 was impeded by the fact that all available TgPVR21 mice were used for the WHO Collaborative Study of TgPVR mice for testing OPV. The producing institute has requested additional support from the WHO and other sources; if mice become available, they will be used to complete this study, comparing a standard D-antigen ELISA test and a rat-immunogenicity test with the Tg-mouse challenge-protection test for estimating potency of IPV preparations. This project was inactive in FY 99 due to unavailability of PVR Tg21 mice needed to conduct further studies. However, the project number and file were retained to allow further development of the test and application of the methods to other projects on IPV in DVP and elsewhere. In FY00, studies on validation of a mouse test for IPV potency in combination vaccines was initiated with personnel in DMA/OTRR. The neutralizing antibody assay validated in TgPVR mice and correlated with protection against disease is now being developed in conventional inbred mice to evaluate immunological interference in combination vaccines. Studies to date show significant interference to the type 1 polivirus response.